Human Cytochrome c Oxidase Analyzed with Cytoplasts

Abstract

The reaction of cytochrome c oxidase (COX) is the final step in human respiration. Although COX has been studied extensively in microorganisms, no tissue-specific functions or bioenergetic disease, such as mitochondrial encephalomyopathy and aging, occur in these organisms. The physiological roles of human COX were analyzed by using cytoplasts (cells without nucleus), ρ° cells (cells without mtDNA), COX mutants, and their cybrids. Recent developments of the Human Genome Project will become an important factor in the study of human bioenergetics. The roles of the COX are not only the generation and regulation of the electrochemical potential (∆μH+) across the inner mitochondrial membrane, but also the regeneration of NAD in mammalian cells. The major subunits I–III (H+ pump) of COX are encoded by mtDNA and the remaining ten minor subunits by nDNA. The cause of the age-dependent decline of COX has been attributed to the accumulation of mutations in mtDNA. However, the involvement of nDNA in the decline is also important because of telomere shortening in somatic cells, and, thus, age-dependent mtDNA expression was analyzed with the cytoplasts. The roles of the control regions of the COX genes are to coordinate both mtDNA and nDNA, depending on the energy demand of the cells.